Automated cryogenic storage and retrieval system

ABSTRACT

A cryogenic storage system includes a transfer module configured to service one or more cryogenic storage freezers. The transfer module includes a working chamber that maintains a cryogenic environment for the transfer of sample tubes between different sample boxes. One or more freezer ports enable the transfer module to receive a sample box extracted from a respective freezer. An input/output (I/O) port enables external access to samples. A box transport robot operates to transport sample boxes between the freezer ports, the working chamber, and the I/O port. A picker robot operates to transfer sample tubes between sample boxes within the working chamber.

RELATED APPLICATION

This application claims the benefit of U.S. Provisional Application No.62/647,450, filed on Mar. 23, 2018. The entire teachings of the aboveapplication are incorporated herein by reference.

BACKGROUND

Cryopreservation is a process essential to maintaining the integrity ofbiological substances over extended periods of storage. At sufficientlylow temperatures, all chemical processes and biological functions ofsuch substances are effectively halted, allowing them to be storedsafely over nearly any length of time. A cryogenic storage freezerenables such storage by providing an insulated and controlled cryogenicenvironment to accommodate a number of biological or other samples. Intypical storage freezers, samples are loaded into racks or trays, eachof which holds several samples. The racks or trays are manually removedfrom the cryogenic environment of the freezer, presenting the rack ortray to a user for removing samples from, or adding samples to, thestorage freezer.

SUMMARY

Example embodiments provide automated storage and retrieval of samplesin a cryogenic environment, as well as automated transfer of individualsamples between sample boxes. Embodiments can provide for maintainingsamples under a cryogenic temperature threshold (e.g., −134° C.) at alltimes, while also enabling access to samples at all times. The samplesmay be organized and tracked by scanning a barcode of each sample.Embodiments may also comprise multiple cryogenic storage freezers andprovide for transfer of sample boxes and individual samples between thestorage freezers, as well as between a storage freezer and aninput/output (I/O) port accessible to a user.

In an example embodiment, a cryogenic storage system includes a transfermodule configured to service one or more cryogenic storage freezers. Thetransfer module includes a working chamber that maintains a cryogenicenvironment for the transfer of sample tubes between different sampleboxes. One or more freezer ports enable the transfer module to receive asample box extracted from a respective freezer. An I/O port enablesexternal access to samples. A box transport robot is configured totransport sample boxes between the freezer ports, the working chamber,the I/O port and other subsystems. A picker robot is configured totransfer sample tubes between sample boxes within the working chamber.

The freezer port can include an ejector configured to transport thefirst sample box through at least a portion of the freezer port to aposition accessible to the box transport robot. The ejector may includea pair of arms configured to clamp opposite sides of the first samplebox. The ejector may also include a floor configured to support a samplebox, where the floor includes one or more portions that are depressiblevia a force applied by the box transport robot. The ejector may also beconfigured to transport a plurality of different sample box formats.

The transfer module may include a transport chamber, the transportchamber being coupled to the freezer port and housing the box transportrobot. The box transport robot may maintain an environment above a glasstransition temperature of the samples being transported through thechamber, and can be connected to the working chamber via an aperture.Alternatively, the transport chamber can be connected to the workingchamber via an intermediate chamber to the aperture, where theintermediate chamber houses at least a portion of the picker robot. Thebox transport robot may be configured to extend into the working chambervia the aperture during transport of a sample box. The picker robot maybe configured to extend into the working chamber via the aperture duringtransport of a sample tube, such as transfer of the sample tube betweensample boxes within the working chamber.

The box transport robot may include a box gripper assembly configured togrip a sample box. The box gripper assembly may include a pair of armsconfigured to clamp opposing corners of the first sample box, where eacharm includes a set of contact points adapted to accommodate a pluralityof sample box formats. One or more of the sets of contact points maydefine a W shape, where a first portion of the W shape accommodates afirst sample box format, and a second portion of the W shapeaccommodates a second sample box format. Alternatively, the contactpoints may terminate in a pair of pins, where the pins are oriented at afirst angle to engage with a first sample box format, and are orientedat a second angle to accommodate a second box format. The box transportrobot may also include a rail assembly on which the box gripper assemblymoves.

The picker robot may include a first arm including a tube gripperassembly and a second arm including a push-up pin. The second arm mayextend under a platform supporting sample boxes in the working chamber,the second arm being configured to drive the push-up pin into the firstsample box to raise a portion of the sample tube from a respectivesample box. The tube gripper assembly may include a plurality of teeth,the tube gripper assembly configured to rotate the plurality of teetharound and toward a center axis to grip the sample tube. The teeth mayalso be used to prevent neighboring sample tubes from rising if frozentogether. The first arm may be configured to move the sample tube to aposition enabling an identification (ID) tag of the sample tube to beread by an ID reader. The position may be internal or external to theworking chamber, and the first arm may rotate the sample tube to alignthe ID tag with the ID reader. The position may enable the ID tag to beread by the ID reader via a reflection of the ID tag from a mirror.

The working chamber may include a platform configured to supportmultiple sample boxes during a transfer of sample tubes between them. Aclamp assembly may be configured to secure a sample box via a forceapplied to a corner of the sample box, the clamp including a set ofcontact points adapted to accommodate a plurality of different samplebox formats. The set of contact points may define a W shape, where afirst portion of the W shape accommodates a first sample box format, anda second portion of the W shape accommodates a second sample box format.The platform may include an aperture exposing a portion of a bottomsurface of a sample box, the aperture enabling access to a bottom of thesample tube by the tube picker robot. The working chamber may be furtherconfigured to contain a liquid coolant below the platform, as well as aheat sink coupled to the platform and configured to be partiallyimmersed in the liquid coolant. The tube picker may include an armsupporting a push-up pin, the arm configured to be at least partiallyimmersed in the liquid coolant.

The transfer module may include a light curtain configured to detect aformat of a sample box at the I/O port. The light curtain may project asingle collimated light source.

The transfer module may also include a plurality of freezer ports, eachof the plurality of freezer ports being configured to receive sampleboxes extracted from a respective freezer. A rail assembly may beconfigured to move the freezer ports between a plurality of freezers.The rail assembly may be further configured to move the working chamber,the box transport robot, and the tube picker robot in unison with the atleast one freezer port. The freezer port may be configured to connectwith an extractor assembly (e.g., an automated rack puller), theextractor assembly being configured to raise a storage rack from afreezer and eject the first sample box from the rack.

A robot in an example embodiment may comprise a box gripper assemblyconfigured to grip a sample box. The box gripper assembly may include apair of arms configured to clamp opposing corners of the sample box, aswell as a pair of contact point sets coupled to a respective one of thepair of arms, each of the contact point sets configured to accommodate aplurality of sample box formats. The robot may further include a robotictransport mechanism configured to move the box gripper assembly. Thefirst set of contact points may define a W shape, where a first portionof the W shape accommodates a first sample box format, and a secondportion of the W shape accommodates a second sample box format. Therobotic transport mechanism may include a rail assembly configured tomove the box gripper assembly laterally and vertically. The robotictransport mechanism may include a robotic arm configured to move the boxgripper assembly.

A robot in a further embodiment may be configured to pick and transfersample tubes. The robot may include a first arm and a second arm. A tubegripper assembly may be coupled to the first arm and include a pluralityof teeth, the tube gripper assembly configured to rotate the pluralityof teeth around and toward a center axis to grip a sample tube. Apush-up pin may be coupled to the second arm, the second arm beingconfigured to drive the push-up pin into a sample box to raise a portionof the sample tube from the sample box prior to engagement by the tubegripper assembly. The robot may further include a motor configured toactuate the tube gripper assembly via an axle extending along the firstarm.

A further embodiment may include a cryogenic sample handling system. Thesystem may include a working chamber configured to maintain a cryogenicenvironment. A platform, housed within the working chamber, may beconfigured to support a plurality of sample boxes. A box transport robotmay be configured to transport a first sample box into and out of theworking chamber. A picker robot may be configured to transport, withinthe working chamber, a sample tube between the first sample box and asecond sample box. The working chamber may be further configured tocontain a liquid coolant below the platform. A heat sink may be coupledto the platform and configured to be partially immersed in the liquidcoolant.

The tube picker robot may include an arm supporting a push-up pin, thearm configured to be at least partially immersed in the liquid coolant.

A method for reading an indicia from a sample container may include,first, picking a sample container in a cryogenic environment using apicker robot. Frost is removed from the sample container while thesample container is at least partially within the cryogenic environment.The indicia may be read from the sample container, and the samplecontainer may then be placed.

Removing the frost may include mechanically removing the frost. Readingthe indicia may occur at least partially in the cryogenic environment.Placing the sample container may include placing the sample containerinto the cryogenic environment. The indicia may be a barcode or at leastone of an alphanumeric character, a graphic, and a symbol. Removing thefrost may include moving the sample container against a frost removaldevice using the picker robot. The frost removal device may be a brushor a blade. The frost removal may occur while the sample container isfully within the cryogenic environment, and while a sample contained inthe sample container is kept below the glass transition temperature ofthe sample. Reading the indicia from the sample container may occurwhile a sample contained in the sample container is kept below the glasstransition temperature of the sample. Reading the indicia from thesample container may include reading the indicia with an optical device,such as a camera.

Further embodiments include methods of picking and transporting anindividual sample box or an individual sample tube implementing one ormore of the operations and/or apparatuses described herein.

Further embodiments may include methods for transporting a sample. Thesample may be removed from a first cryogenic environment. The sample maybe placed into a second cryogenic environment wherein the secondcryogenic environment is contained within an mobile apparatus. Thesample may then be moved from a first sample receptacle to a secondsample receptacle within the second cryogenic environment. The mobileapparatus may be automated. At least one of the removing the sample fromthe first cryogenic environment and the placing the sample into thesecond cryogenic environment may occur while the sample is kept belowthe glass transition temperature of the sample. The first and secondcryogenic environments may be independently maintained.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particulardescription of example embodiments, as illustrated in the accompanyingdrawings in which like reference characters refer to the same partsthroughout the different views. The drawings are not necessarily toscale, emphasis instead being placed upon illustrating embodiments.

FIGS. 1A-I illustrate an automated cryogenic storage system and relatedcomponents in an example embodiment.

FIG. 2 is a block diagram of a cryogenic storage system including acontroller in a further embodiment.

FIG. 3 is a flow diagram illustrating a process of transferringindividual samples in one embodiment.

FIG. 4A-B illustrate a box transport robot in one embodiment.

FIGS. 5A-B illustrate a gripper assembly for a box picker robot.

FIGS. 6A-C illustrate the gripper assembly configured to grip a range ofdifferent box formats.

FIGS. 7A-B illustrate a box gripper in a further embodiment.

FIGS. 8A-D illustrate a freezer port in one embodiment.

FIG. 9 illustrates an automation station in one embodiment.

FIGS. 10A-B illustrate an I/O module in one embodiment.

FIGS. 11A-C illustrate a working chamber in one embodiment.

FIGS. 12A-H illustrate a tube picker in one embodiment.

FIG. 13 illustrates a tube extraction operation in one embodiment.

FIG. 14A-B illustrate a sample ID scan operation in one embodiment.

FIG. 15 illustrates a system implementing multiple freezers.

FIGS. 16A-C illustrates a system in a further embodiment.

DETAILED DESCRIPTION

A description of example embodiments follows. The teachings of allpatents, published applications and references cited herein areincorporated by reference in their entirety.

FIGS. 1A-F illustrate an automated cryogenic storage system 100 andcomponents in an example embodiment. FIG. 1A shows a perspective view ofthe system 100, which includes a transfer module 101, a freezer 105 a,and a rack puller 107 a. The freezer 105 a is a storage freezer thatmaintains a cryogenic environment for storing multiple samples, such assample tubes assembled in sample boxes. In the illustrated embodiments,the freezer 105 a is a cylindrical vessel; however, the freezer can haveany shape such as, for example, a rectangular box. In some preferredembodiments, freezer 105 a includes an external wall or shell separatedfrom an inner wall or shell by a vacuum insulated space (e.g., a dewarvessel). The rack puller 107 a may be mounted to the top of the freezer105 a, and operates to raise a selected storage rack from the freezer105 a. Once raised, a sample box can be added or removed from the rack,and the rack puller 107 a may then replace the rack into the freezer 105a. Alternatively, the rack puller 107 a may be mounted to the transfermodule 101, and the rack puller 107 a may be selectively positioned tooperate with the freezer 105 a as well as one or more other freezers(not shown). Example freezers and rack pullers that may be implementedin the system 100 are described in further detail in U.S. patentapplication Ser. Nos. 15/085,431 and 15/085,630, the entire teaching ofwhich are incorporated herein by reference.

The transfer module 101 operates to transfer sample boxes, as well asindividual sample tubes, between locations while maintaining thosesamples below a respective glass transition temperature T_(G) (e.g.,−134 C), thereby maintaining the integrity of those samples. Forexample, the module 101 may transfer sample boxes between the freezer105 a, additional freezers (not shown), and an input/output (I/O) port125, and may transfer sample tubes between those boxes. The I/O port 125may be configured to accept a portable storage unit (not shown) storingone or more sample boxes, and a user may insert and remove the portablestorage unit via an I/O door 199. An example portable storage unit thatmay be implemented with the system 100 is described in further detail inU.S. patent application Ser. No. 14/600,751, the entire teaching ofwhich are incorporated herein by reference.

The transfer module 101 may also relocate in order to service otherfreezers (not shown) in addition to the freezer 105 a. A cart 190supports the transfer module 101, and enables the module to move along atrack 192. The cart 190 may be propelled automatically by a motorassembly in response to a movement command, or may be moved by a user.Thus, in further embodiments described below, wherein the transfermodule 101 services multiple freezers, the cart 190 and track 192enables the transfer module 101 to relocate to each of those multiplefreezers. In further embodiments, a motion system for the transfermodule 101 may be configured above the module 101 in addition to (or inplace of) the cart 190 and track 192. Further, in place of the track192, the module 101 may be moved using a trackless motion system thatuses a local positioning system (e.g., GPS, WiFi, optical (e.g. camerabased), radar, lidar, floor or freezer mounted sensors). Propulsion canbe provided to the transfer module by any known motion system, such ason-board motors that drive wheels or gears, in floor linear motors,off-board motors that drive cables or gears, or an overhead gantrysystem.

FIG. 1B illustrates a front view of the system 100. Here, thedisposition of the transfer module 101 is shown in further detail. Thetransfer module 101 may include three chambers: a transport chamber 110,an intermediate chamber 115, and a working chamber 120. The chambers110, 115, 120 may be coupled to one another in series, and passagebetween the chambers may be selectively enabled via automated doors (notshown). The transport chamber 110, in both FIGS. 1A and 1B, is shown ina cutaway view to illustrate components internal to the chamber 110,including a box transport robot 130. The transport chamber 110 may beclosed as shown in FIG. 1E, which may contribute to preserving thetemperature of the samples below a glass transition temperature. The boxtransport robot 130 operates to transport sample boxes between thefreezer 105 a, the I/O port 125, the working chamber 120, which itaccesses by passing through the intermediate chamber 115, and additionallocations. A freezer port 108 a facilitates the transfer of sample boxesbetween the freezer 105 a and the transfer module 101. In particular,the rack puller 107 a, after raising a storage rack from the freezer 105a, may propel the sample box into the freezer port 108 a. The freezerport 108 a, in turn, may position the sample box for pickup by the boxtransport module 130. Conversely, when returning or storing a sample boxto the freezer 105 a, the freezer port 108 a may propel the sample boxtoward the rack puller 107 a, where it is added to a rack before therack puller 107 a lowers the rack into the freezer 105 a. The freezerport 108 a may be mounted to the freezer 105 b and couples to thetransport chamber 110 when the transfer module 101 is positioned toaccess the freezer 105 a. In such a configuration, the transport chamber110 may include a port (e.g., an aperture) for connecting to the freezerport 108 a, or may include a component of the freezer port 108 a.Alternatively, the freezer port 108 a may be mounted to the transportchamber 110, and aligns with the rack puller 107 a when the transfermodule 101 is positioned to access the freezer 105 a.

The working chamber 120 maintains a cryogenic environment, and enablesthe selection and transfer of individual sample tubes between sampleboxes. In contrast, the intermediate chamber 115 and transport chamber110 may maintain temperatures and humidity above that of a cryogenicenvironment. For example, the transport chamber 110 may be configuredabsent active temperature or humidity control, and, thus, may maintain atemperature comparable to room temperature. The intermediate chamber 115may be configured similarly. However, both chambers 110, 115 may becooled and/or dehumidified via convection from the cryogenic environmentof the working chamber 120 and/or other cooling and/or dehumidifyingmethods. In further embodiments, the module 101 may include chambers ina different configuration. For example, a single chamber may encompassboth the transport chamber 110 and intermediate chamber 115, or theintermediate chamber 115 may be omitted, the transport chamber 110 beingcoupled directly to the working chamber.

FIG. 1C shows a cross-section view of the transport module 101. Here, asecond freezer port is shown 108 b for servicing a freezer on anopposite side of the module 101 from the freezer 105 a. The workingchamber 120, as indicated above, is configured to maintain a cryogenicenvironment, thereby preserving the temperature of the samples within itbelow a respective glass transition temperature T_(G) of the samples(e.g., −134 C). To facilitate this environment, an insulated wall 122encompasses the bottom and sides of the chamber 120, and the top of thechamber 120 may be substantially isolated from the intermediate chamber115 (e.g., via a removable cover or door) when sample boxes are notbeing transferred into or out of the working chamber 120. The workingchamber 120 houses a platform 121 that supports multiple sample boxesand configurations, which are moved into and out of the working chamber120 by the box transport robot 130.

The intermediate chamber 115 houses operational machinery as describedin further detail below, including the picker robot 140. The pickerrobot 140 operates to transfer individual sample tubes between sampleboxes within the working chamber 120. The picker robot 140 substantiallyresides in the intermediate chamber 115, extending partially into theworking chamber 120 during a sample transfer operation. As a result, thepicker robot 140 may avoid adverse effects of exposure to the cryogenicenvironment of the working chamber 120.

FIG. 1D illustrates a side view of the system 100. Here, an I/O shield126 is shown more clearly. The I/O shield 126 may be coupled to one orboth of the I/O port 125 and the transport chamber 110, and serves as apassageway between them. When the box transport robot 130 adds orremoves a sample box from the I/O port 125, it extends through the I/Oshield 126. The I/O shield 126 therefore may protect the sample box androbot 130 from interference. The I/O shield 126 may also include aremovable cover or door at the threshold of the transport chamber 110 toreduce gas transfer between the transport chamber 110 and the externalenvironment.

FIG. 1E illustrates the transfer module 101 in a further view. Here, thetransport chamber 110 is shown with its enclosure intact, and a fillstation 194 may be located at the front, rear or side of the module 101,and is described in further detail below with reference to FIGS. 1G-I.The fill station 194 may connect to a liquid coolant source, and directsa liquid coolant (e.g., a cryogenic fluid such as liquid nitrogen) tothe working chamber 120 where it cools the working chamber to acryogenic temperature.

FIG. 1F illustrates an example storage rack 185 and sample boxes 180 a-bthat may be implemented in the system 100. The system 100 may beconfigured to store and transfer sample boxes of multiple differentformats. For example, sample boxes 180 a and 180 b, shown in top-downview, correspond to a Society for Biomolecular Screening (SBS) standardformat box and a Cryobox standard format box, respectively. Each samplebox 180 a-b includes multiples slots for storing samples, such as sampletubes 182 a-b.

The storage rack 185 includes multiple rack slots (e.g., rack slot 186)for storing respective sample boxes. The freezer 105 a may storemultiple storage racks resembling the storage rack 185, and the rackpuller 107 a may raise the storage rack 185 from the freezer 105 a byengaging with an interface 188 mounted to the top of the storage rack188. To accommodate storage of sample boxes in different formats, therack slot 186 may be adapted to accommodate the largest box format(e.g., sample box 180 b, Cryobox), and may optionally include a stopper187 positioned to accommodate a smaller box format (e.g., sample box 180a, SBS). The stopper 187 may prevent the sample box 180 a from moving tothe rear of the storage rack 185, thereby maintaining a face of thesample box 180 a at a front face of the storage rack 187. The stopper187 may be omitted from slots accommodating the larger box format, ormay be shaped to allow passage by the larger box format. As a result,the storage rack 185 can store and present the sample boxes 180 a-b in auniform manner. Alternatively, to provide greater storage capacity andmaximize use of space within a freezer, the storage rack 187 may beadapted to accept a single, uniform box format and orientation.

FIGS. 1G-1I illustrate the fill station 194 in further detail. FIG. 1Gis a perspective view of the fill station 194. A receiver 196 may extendfrom the transfer module 101 to receive a liquid coolant for cooling theworking chamber 120, and is covered by a receiver cap 197. A nozzleassembly 191 may extend from a liquid coolant source, and may beintegrated into a wall proximate to the receiver 196 when the transfermodule 101 is at a particular location. A controller (e.g., controller195 described below) may control the flow of the coolant to the workingchamber 120 based on a detected temperature and/or other conditions atthe working chamber 120. The controller may control a valve or othercomponent controlling flow at the nozzle assembly 191, and may beintegral to the wall and/or an access panel (e.g., access panel 1510described below).

Prior to a transfer of liquid coolant, the nozzle assembly 191 maydescend onto the receiver 196. The nozzle assembly includes an extension193 projecting downward such that, during the descent, the extension 193may contact the receiver cap 197 and cause the receiver cap 197 to swingopen and to the side, exposing the top of the receiver 196 as shown inthe side view in FIG. 1H. The nozzle assembly 191 may continue todescend until it is coupled with the receiver 196, as shown in thecross-section view of FIG. 1I. Once coupled, the nozzle assembly 191 maytransfer the liquid coolant to the receiver 196 as indicated by thearrow in FIG. 1I.

FIG. 2 is a block diagram of the cryogenic storage system 100 configuredwith a controller 195 in a further embodiment. As shown, the system 100includes a second freezer 105 b, which can be selectively coupled to thetransfer module 101 via the freezer port 108 b. The controller 195 maybe connectively coupled to the transfer module 101 and the freezers 105a-b, and may generally control some or all of the operations of each.For example, the controller 195 may control the freezers 105 a-b andrespective rack pullers 107 a-b to retrieve and replace selected sampleboxes (e.g., sample boxes 180 a-b) to and from the freezers 105 a-b. Thecontroller 195 may also control the transfer module 101 to transportsample boxes between the freezer ports 108 a-b, the I/O port 125, andthe working chamber 120, and to transfer sample tubes between sampleboxes in the working chamber 120. Further, the controller 195 maymonitor and control refrigeration and humidity levels of the transfermodule 101 (particularly the working chamber 120) and the freezers 105a-b, and may control other operations such as calibration of mechanicalcomponents, identifying samples, and failure or disaster recovery. Thecontroller 195 may also maintain a database 198 storing informationregarding the samples stored within the working chamber 120 and freezers105 a-b, including the location of each sample within the freezers 105a-b. The controller 195 may update the database 198 in response to thetransfer of samples into or out of the freezers 105 a-b.

To provide such control operations, the controller 195 may includesuitable computer hardware and software resources, such as one or morecomputer workstations and an interface configured for communication withthe transfer module 101 and freezers 105 a-b. The controller 195 mayalso include an interface (e.g., a workstation) allowing a user tomonitor the system 100 as well as monitor and/or control theaforementioned operations of the system 100.

FIG. 3 is a flow diagram illustrating a process 300 of transferringsamples, which may be carried out by the system 100 described above withreference to FIGS. 1A-E and 2. With reference to FIG. 2 , the controller195 may parse a transfer order, which specifies one or more sample tubes(e.g., sample tubes 182 a-b) and/or sample boxes (e.g., sample boxes 180a-b) to be transferred (305). The transfer order may specify one or moreof an origin, a destination, and one or more sample identifiers (IDs)that identify a sample box 180 a and/or sample tubes. For example, atransfer order may specify:

-   -   a) storage of a sample box 180 a at the I/O port 125 to a        specified or unspecified freezer (e.g., freezer 105 a),    -   b) retrieval of a specified storage box or sample tube to the        I/O port 125,    -   c) transfer of a specified sample box 180 a to a specified        freezer,    -   d) retrieval of a specified individual or set of sample tubes to        the I/O port 125,    -   e) transfer of specified sample tubes between sample boxes, or    -   f) transfer of the contents of a specified freezer to another        freezer or the I/O port 125.

Based on the transfer order, the controller may determine the origin anddestination of the samples to be transferred (310). To do so, thecontroller 195 may refer to the database 198 to determine the presentlocation of the samples, and/or may cause the transfer module 101 toperform a scan of the samples (e.g., via an ID reader) to determine therespective sample IDs. With this information, the controller 195 maythen map a route to be taken by the box transfer robot 130 to carry outthe transfer (315). If the transfer requires a transfer in individualsample tubes between sample boxes, then the controller 195 may commandthe box transport robot 130 to transport one or more sample boxes to theworking chamber 120 (320). For example, the controller 195 may commandthe box transport robot 130 to 1) pick up a sample box 180 a at thefreezer port 108 a and transport it to a selected support surface in theworking chamber 120, and 2) pick up a second sample box at the I/O port125 and transport it to another selected support surface in the workingchamber 120. The controller 195 may also command the freezers 105 a-band rack pullers 107 a-b to retrieve and produce the sample boxes at therespective freezer ports 108 a-b.

In order to transfer sample tubes between sample boxes, the controller195 may map a route to be taken by the picker robot 140 within theworking chamber 120 (325). In doing so, the controller may refer to thedatabase 198 to determine the location of each sample tube within thesample boxes, as well as available slots within the sample boxes. Thecontroller 195 then commands the picker robot 140 to operate accordingto the mapped route to effect the transfer of the sample tubes betweenthe sample boxes (330). The picker robot 140, when transferring eachsample tube, may also route the sample tube to a brush to remove frostfrom the sample tube followed by an ID reader (located, e.g., in theintermediate chamber 115) to confirm the sample ID of the sample tube.Once the sample tubes are relocated to their target sample boxes, thecontroller 195 may then command the box transport robot 130 to transportthe sample boxes from the working chamber 120 toward theirdestination(s) (e.g., the freezer ports 108 a-b, the I/O port 125)(335). The controller 195 may also command the freezers 105 a-b and rackpullers 107 a-b to accept sample boxes deposited to the freezer ports108 a-b, place those boxes into a designated slot 186 in a storage rack185, and return the storage rack 185 to the respective freezer 105 a-b.The controller 195 may then update the database 198, based on thetransfer, to indicate the updated location of each of the samples and/orsample boxes involved in the transfer.

Alternatively, if the transfer order 305 does not require a transfer ofsample tubes between sample boxes, then the controller 195 may commandthe box transport robot 130 to transport the samples boxes directly fromtheir origin to their destination, without first locating to the workingchamber 120. In such a transfer, the operations 320-335 may be omitted.

FIG. 4A-B illustrate the box transport robot 130 in further detail. FIG.4A is a perspective view of the box transport robot 130 within thetransport chamber 110. The box transport robot 130 is mounted to anautomated rail assembly 132, which provides for lateral movement of therobot 130 along the rails 133 a-b of the assembly 132. For example, thebox transport robot 130 may move in the x direction along the rail 133a, and along the y direction along the rail 133 b, enabling the boxtransport robot 130 to move to locations above the I/O port 125 and theintermediate chamber 115. The box transport robot 130 may be housedwithin an enclosure 131 (e.g., a windowed enclosure as shown), andincludes a vertical driver 134 and a gripper assembly 135. The verticaldriver 134 may include one or more stepper or servo motors and isconfigured to raise and lower the gripper assembly 135 along a verticaltrack to a distance sufficient to reach the freezer ports 108 a-b, theI/O port 125, and the working chamber 120. Alternatively, the verticaldriver may include an extendable arm (e.g., a telescoping arm) capableof lowering the gripper assembly as described above. The gripperassembly 135 is configured to engage with sample boxes such as thesample box 180 b as shown, enabling the box transport robot to transportthe sample box 180 b.

FIG. 4B is a front cross-section of the box transport robot 130. Here,the gripper assembly 135 is engaged with the sample box 180 b and hasraised the sample box 180 b into the enclosure 131. In doing so, thesample box 180 b may be protected during transport within the transfermodule 101, and the enclosure 131 may also function as a heat shield andconvection blocker to reduce the heat absorbed by the sample box 180 a-bduring transport.

FIGS. 5A-B illustrate the gripper assembly 135 in further detail. FIG.5A is a perspective view, and FIG. 5B is a front view. The gripperassembly 135 includes a pair of gripper arms 138 a-b that canselectively engage and secure a sample box, such as the sample box 180 aas shown, by closing toward the center of the sample box 180 a andcontacting opposite corners of the sample box 180 a. In furtherembodiments, the gripper assembly 135 may implement one or moreadditional arms, which may be configured to secure additional cornersand/or edges of the sample box 180 a. A cover 137 can be selectivelylowered onto a top surface of the sample box 180 a once secured by thegripper arms 138 a-b. When in close proximity to the top of the samplebox 180 a-b, the cover 137 may secure the sample tubes within the samplebox 180 a-b, and may also serve as a heat shield and minimize frostbuildup at the sample tubes. A motor assembly 136 controls operation ofthe gripper arms 138 a-b and cover 137, and may include a motorconfigured to drive the gripper arms 138 a-b inward toward the center ofthe gripper assembly 135, as well as outward from the center whenreversed. Alternatively, the motor assembly 136 may be replaced by agear assembly that is controlled by a motor set coupled to the gearassembly and located farther from the gripper arms 138 a-b. As a result,the motors operating the gripper assembly 135 can be further isolatedfrom the working chamber 120, thereby minimizing adverse effects of thecryogenic environment on the motors.

FIGS. 6A-C illustrate the gripper assembly configured to secure a rangeof different sample box formats and orientations. FIG. 6A is aperspective view of the gripper assembly 135 gripping sample boxes inthree different configurations 601, 602, 603. In the first configuration601, the gripper assembly 135 is configured to engage with the samplebox 180 a (e.g., a rectangular SBS format box). In the secondconfiguration, the gripper assembly 135 is configured to engage with thesame sample box 180 a, but oriented 90° from the first orientation. Inthe third configuration, the gripper assembly 135 is configured toengage with the sample box 180 b (e.g., a square Cryobox format box). Inorder to secure the respective sample box in each configuration(adjusted to a known rotational and positional orientation), the gripperassembly 135 may rotate to a position such that its gripper arms 138 a-bare both at opposite corners of the sample box and are aligned such thateach of gripper arms 138 a-b can apply a force toward the center of thesample box. As a result of such positioning, the gripper arms 138 a-bmay close in to secure the respective sample box. The pair of gripperarms 138 a-b may also operate to adjust the sample box to a targetrotational and positional orientation. Thus, the gripper assembly 135may rotate to adjust between the grip positions for different boxformats (e.g., SBS and Cryobox), allow the pickup of differentorientations of a sample box (e.g., two orientations of an SBS formatbox), and rotate to allow the barcode reader to read any or all sides ofthe sample box.

FIG. 6B and FIG. 6C illustrate the configurations 601-603 in top-downand bottom-up views, respectively. Here, in the top-down view of FIG.6B, the gripper arms 138 a-b are shown to include respective contactmembers 139 a-b. Each of the contact members 139 a-b may form a pair ofarms extending perpendicular to one another, where each arm includes acontact point (e.g., a pin) extending vertically from the arm. Whensecuring the sample boxes 801 a-b, the gripper arms 138 a-b may berotated into position as described above, and then closed in toward thecenter of the sample boxes 180 a-b. When the gripper arms 138 a-b arefully closed in, the contact members 139 a-b make contact with twoadjoining edges of the sample box 180 a-b via the set of contact points,and each gripper arm 138 a-b may apply a force toward the center of thesample boxes 180 a-b sufficient to secure the sample boxes 180 a-bwithin the gripper arms 138 a-b. As shown in FIG. 6C, the contact member139 a-b may also extend partially underneath the sample boxes 180 a-bwhen contact is made, thereby supporting the sample box 180 a-b frombelow to further secure the sample boxes 180 a-b during transport.

FIGS. 7A-B illustrate an alternative embodiment of the gripper assembly135, wherein the gripper arms 138 a-b each include a W-shaped contactmember 139 c-d in place of the contact members 139 a-b described above.Each W-shaped contact member 139 c-d may include two (or more) squarenotches, where each notch is adapted to secure a corner of a sample boxin one or more particular formats or orientations. Three configurations701, 702, 703 may be comparable to the configurations 601-603 describedabove. However, in order to align the contact member 139 c-d for contactwith a given sample box 180 a-b, the gripper assembly 135 aligns thegripper arms 138 a-b to the corners of the sample boxes 180 a-b to oneof the notches of the contact members 139 c-d before closing in tosecure the sample boxes 180 a-b. For example, in configuration 701, therightmost notch of contact member 139 c and the leftmost notch ofcontact member 139 d are aligned to contact opposite corners of thesample box 180 a. In contrast, in configuration 702, the leftmost notchof contact member 139 c and the rightmost notch of contact member 139 dare aligned to contact opposite corners of the sample box 180 a in anorientation rotated 90 degrees. As shown in FIG. 7B, the contact members139 c-d may include a lip 730 extending below the sample boxes 180 a-bwhen secured.

FIGS. 8A-D illustrate the freezer port 108 a in further detail. FIG. 8Ais a perspective view of the freezer port 108 a, which may connect withthe rack puller 107 a and provide for loading and unloading a sample box(e.g., sample box 180 a as shown) to and from a storage rack (e.g.,storage rack 185) loaded into the rack puller 107 a. The freezer port108 a may also be referred to as an ejector, and includes a pair ofpushers 830 a-b. When ejecting the sample box 180 a from the rack puller107 a, the pair of pushers 830 a-b may push opposite sides of the samplebox 108 a to keep the sample box 108 a secure while moving it along aguided passageway to a platform 820. The pusher 830 a may be locatedpartially at the rack puller 107 a, and may extend from the rack puller107 a into the freezer port 108 a. Once positioned properly at theplatform 820, the sample box 180 a may be picked up by the box transportrobot 130, via the gripper arms 138 a-b, for transport. When returning asample box 180 a to the rack puller 107 a, the pushers 830 a-b may pushthe sample box 180 a from the platform 820, along the guided passageway,to the rack puller 107 a. As the sample box 180 a is pushed, bothpushers 830 a-b may maintain contact with the sample box 180 a for boxstability.

FIGS. 8B and 8C illustrate the freezer port 108 a in operation ofhandling sample boxes in further orientations and formats. FIG. 8B showsfreezer port 108 a with the sample box 180 a in an orientation turned90° from the orientation shown in FIG. 8A. FIG. 8C shows the freezerport 108 a with the sample box 180 b. By applying pushers 830 a-b atopposite sides of the sample boxes 180 a-b, the freezer port 108 a canaccommodate a range of different sample box formats and orientations.

FIG. 8D illustrates the platform 820 in further detail. When gripping asample box, the box transport robot 130 may position a portion of thegripper arms 138 a-b partially under the sample box as described above.In order to accommodate this positioning, the platform 820 may includedepressible segments 822 a-b. The depressible segments 822 a-b may besupported by respective springs such that they support a sample box, butcan be lowered by a downward force applied by the gripper arms 138 a-b.

FIG. 9 illustrates an automation station 900 in one embodiment. Theautomation station 900 may be located at a floor 915 occupying a bottominterior surface of the intermediate chamber 115, and is positionedabove the working chamber 120. The floor 915 enables passage to theworking chamber 120 via an aperture 926, which may be selectively openedand closed via automated doors 925 a-b. The doors 925 a-b may remainclosed outside of a transfer operation or sample access (e.g., picking,consolidating or tube identification operations), thereby minimizingheat transfer to the working chamber 120 and maintaining the cryogenicenvironment within it. An ID reader 930 may include one or more scanners(e.g., a barcode reader, a QR code scanner) configured to read a sampleID from a sample tube presented to it.

The picker robot 140 may include a number of components occupying theautomation station 900. Specifically, the picker robot 140 may include atube picker 142 that is mounted to an automated rail assembly 141, whichprovides for lateral and vertical movement of the tube picker 142. Therail assembly 141 may include three rail subassemblies 952, 953, 954,where each of the subassemblies controls movement of the tube picker 142in a respective x, y and z direction. In particular, the tube picker 142may be mounted to a vertical rail subassembly 952 for moving the pickerrobot in the z direction. The vertical rail subassembly 952, in turn,may be mounted to a first lateral rail subassembly 953 for movement inthe x direction. Lastly, the first lateral rail subassembly 953 may bemounted to a second lateral rail subassembly 954 for movement in the ydirection. In alternative embodiments, the tube picker 142 may bemounted to a robot arm or other automated mechanism for controlling themovement of the tube picker 142.

FIGS. 10A-B illustrate an I/O module 950. FIG. 10A is a perspectiveview, while FIG. 10B is a front view. The I/O module 950 may residewithin the I/O port 125 (FIG. 1A), and is configured to scan a receivedsample box to determine a format and/or orientation of the box. Whenreceiving a sample box at the I/O port 125, a user may place the samplebox on a movable stage 960 as it moves along a rail 962 to pass througha light curtain 965. The light curtain 965 may include a light source966, a lens 967, and light sensors 968. The light source 967 may be asingle light source that is collimated by the lens 967 (e.g. a Fresnellens) to project a collimated light beam across the rail 962 where itmay be detected by the sensors 968 (e.g., a set of light sensorsarranged in a vertical series). As a result of the light beam beingcollimated, an object blocking the beam may be detected and measuredsubstantially accurately regardless of distance from the light source966. The beam of light may also be oriented diagonally to the path ofthe sample box as shown in FIG. 10A, thereby positioning the lightcurtain 965 to measure a diagonal length of the sample box as it passesthrough the light curtain 965. An example light curtain that may beimplemented in the I/O module 950 is described in further detail in PCTApplication No. PCT/IB2018/050705, the entire teachings of which areincorporated herein by reference.

When the light beam is blocked by the passing sample box, the signaldetected by the sensors 968 can be interpreted to determine the heightof the labware. For example, the sensors 968 may detect a single sampletube raised above a height threshold for the labware type. In response,the system may be alerted that a sample tube is seated improperly withina sample box, and can take corrective action to reposition the sampletube (e.g., returning the stage 960 to its starting position andalerting the user). A signal detected by the sensors 968 (e.g., avoltage or current over time as a sample box is passed through the lightcurtain, or a digital signal) may also be interpreted to determine theformat and/or orientation of the sample box (e.g., SBS or Cryoboxformat). Based on the detected format and orientation, the module 101may command the box transport robot 130 to configure its gripper arms138 a-b to properly engage with the sample box, and the box transportrobot 130 may then pick up and transport the sample box from the I/Omodule 950 to the working chamber 120 or a freezer port 108 a-b Infurther embodiments, the I/O module may also include an ID reader (e.g.,a barcode scanner) to read a sample ID of the sample box or sampletubes.

FIGS. 11A-C illustrate the working chamber 120 in further detail. FIG.11A is a front cross-section of the working chamber 120. The workingchamber 120, as described above, is configured to maintain a cryogenicenvironment, thereby preserving the temperature of the samples within itbelow a respective glass transition temperature T_(G) of the samples(e.g., −134 C). To facilitate this environment, an insulated wall 122encompasses the bottom and sides of the chamber 120, and the top of thechamber 120 may be substantially isolated from the intermediate chamber115 via the automated doors 925 a-b that can cover the aperture 926 whensample boxes are not being transferred into or out of the workingchamber 120 and when the samples are not being moved. The workingchamber 120 houses a platform 121 that supports multiple sample boxes,which are moved into and out of the working chamber 120 by the boxtransport robot 130. The working chamber 120 may hold a volume of aliquid coolant (e.g., a cryogenic fluid such as liquid nitrogen) at aportion of the working chamber 120 below the platform 121. A push-up arm144, terminating in a push-up pin 143, is an extension of the pickerrobot 140 (described in further detail below), and may be partiallyimmersed in the liquid coolant. In such a configuration, a portion ofthe push-up arm 144, particularly a vertical shaft portion extending outof the working chamber 120, may be composed of a material and structureto provide a low heat transfer, thereby reducing heat exchange betweenthe liquid coolant and the environment external to the working chamber120. Alternatively, the working chamber 120 may include a subchamberconfigured to contain the liquid coolant, or implement an alternativecooling mechanism (e.g., a heat exchanger) to maintain the cryogenicenvironment.

FIG. 11B is a perspective view of components internal to the workingchamber 120. Here, the platform 121 is shown to include a set of supportsurfaces 127 a-d for accepting and securing respective sample boxes. Asshown, each of the support surfaces 127 a-d is occupied by a sample boxof a Cryobox format (e.g., sample box 180 b). Clamps 128 a-d may eachapply a clamping force at a respective support surface 127 a-d to securethe sample box in place. Further, heatsinks 123 a-d may be coupled toouter edges or underside of the platform 121 and may extend verticallyfrom the platform 121. The heatsinks 123 a-d can assist in maintainingthe cryogenic environment within the working chamber 120 andparticularly the environment above the sample boxes, into which thesample tubes may be raised (by the picker robot 140) for transfer orscanning. The heatsinks 123 a-d may also extend below the platform 121,and may be partially immersed in the liquid coolant occupying a volumebelow the platform 121. A brush 932 is described in further detail belowwith reference to FIG. 14A.

FIG. 11C is a top-down view of the platform. In contrast to FIG. 11B,support surfaces 127 a-b are occupied by sample box in an SBS format(e.g., sample box 180 a), while support surfaces 127 c-d are occupied bysample boxes in a Cryobox format (e.g., sample box 180 b). Sample boxesof either format can be supported at each of the support surfaces 127a-d. Each of the clamps 128 a-d may terminate in 2 square notches asshown (e.g., a W shape comparable to the contact members 139 c-ddescribed above), where each notch is adapted to secure a corner of asample box in one or more particular formats or orientations. Thus, whenthe clamps 128 a-d apply a force toward a raised center guide(s) 129,they can make contact with a corner of a respective sample box at one ofthe notches, thereby securing the box regardless of format ororientation. The clamps 128 a-d may be actuated by motors locatedexternal to the working chamber 120, which transfer a torque to a rackand pinion of the clamps 128 a-d via respective rods 1115 a-d.

To enable access to individual sample tubes within the sample boxes, theplatform 121 may define one or more apertures, such as aperture 124. Theapertures may extend to some or all of the support surfaces 127 a-d toexpose at least a portion of the bottom surface of a sample box whenoccupying the support surfaces 127 a-d. As a result, the picker robot140, operating the push-up arm 144 (FIG. 11A) below the platform 121,can insert the push-up pin 143 through the sample box to raise aselected sample tube partially out of the sample box, therebyfacilitating access to the sample tube. Some or all of the supportsurfaces 127 a-d may not include apertures that enable access to allsample tubes by the push-up pin 143, due to the need to adequatelysupport the sample box at the platform 121. In such a case, the boxtransport robot 130 may lift, rotate and replace the sample box to itssupport surface 127 a-d, or may move the sample box to another supportsurface 127 a-d to expose a different portion of the bottom of thesample box to the push-up pin 143.

FIGS. 12A-G illustrate a tube picker 142 in further detail. The tubepicker may be mounted to the rail assemblies 952-954, described abovewith reference to FIG. 9 , for movement in the x, y and z directions.FIG. 12A is a perspective view of the tube picker 142 including a frostshield 1210. Because the tube picker 142, and particularly the lowerportion of the tube picker 142, is periodically lowered into thecryogenic environment of the working chamber 120, it is susceptible to abuildup of frost. The frost shield 1210 covers the lower portion of thetube picker 142 to minimize the buildup of frost on the componentshoused within.

FIG. 12B is a perspective view of the tube picker 142 absent the frostshield 1210. A motor 1220 operates to actuate a gripper head 1225 at anopposite end of the tube picker 142. Due to the cryogenic environment inwhich the gripper head 1225 operates, the motor 1220 (and other poweredcomponents) may be located remotely from the gripper head 1225 in orderto prevent adverse effects on the motor 1220. A pair of support rods1230 a-b may extend between the motor 1220 and the gripper head 1225 tosupport the assembly. A shaft 1250, powered by the motor 1220, actuatesthe gripper head 1225.

FIGS. 12C and 12D show the gripper head 1225 in a perspective view and across-section, respectively. The shaft 1250 connects to a first gear1252, which meshes with a second gear 1262 that rotates around a centerpin 1260. The second gear 1262 is also coupled to a cam plate 1264,which is retained by a retainer 1266.

FIGS. 12E-G are cross-sections of a bottom-up view of the gripper head1225, and are ordered to illustrate operation of the gripper head 1225.At FIG. 12E, the first gear 1252, driven by the motor 1220, rotates thesecond gear 1262, which also rotates the cam plate 1264. As shown inFIG. 12F, pins 1272 a-c, coupled to teeth 1274 a-c, move radially alongrespective tracks 1270 a-c as the cam plate 1264 rotates. FIG. 12G showsin further detail the set of gripper teeth 1274 a-c (also referred to astube clamps), which engage with a sample tube (e.g., sample tube 182 a).One end of each of the teeth 1274 a-c is pinned to a plate of thegripper head 1225, while an opposite end is coupled to a respective oneof the pins 1272 a-c. Thus, as a result of the pins 1272 a-c movingalong the respective track 1270 a-c, the teeth 1274 a-c rotate at oneend toward a center of the gripper head 1225 providing a horizontalgripping force, thereby making contact with a sample tube aligned at thegripper head 1225. The gripper head 1225 can be configured to support avariety of sample tube diameters (e.g., by advancing the teeth 1274 agiven distance corresponding to a selected tube diameter) without theneed for tool changes. Further, the teeth 1274 a-c may be thermallyisolated (e.g., via an insulating material, such as a gap of air) fromthe components that bridge into the intermediate chamber, therebyreducing heat transfer to a gripped sample tube.

FIG. 12H is a further bottom-up view of the gripper head 1225,illustrating the teeth 1274 a-c in a fully engaged state. A pusher pin1280 may occupy a center of the gripper head 1225 directly above theteeth 1274 a-c. The pusher pin 1280 may be actuated by the motor 1220(e.g., via the center pin 1260), and operates to separate a sample tubefrom the teeth 1274 a-c when disengaging the sample tube. The pusher pin1280 may be sized, as shown, to pass through the teeth 1274 a-c evenwhen fully engaged, and may include fins as shown to facilitate contactwith the sample tube. The pusher pin 1280 can assist in placing andpositioning a sample tube in a target slot of a sample box, and can alsocounteract binding between the teeth 1274 a-c and the sample tube as aresult of frost.

FIG. 13 illustrates a portion of a tube picker robot 140 in an operationof extracting a sample tube 182 b from a sample box 180 b in the workingchamber 120. The gripper head 1225 and push-up pin 143 may first bepositioned directly above and below, respectively, the target sampletube 182 b. The push-up arm 144, which may be driven by the railassemblies 953, 954 (FIG. 9 ) to move laterally in unison with thegripper head 1225, may then raise the push-up pin 143 up through theplatform 121 and the sample box 180 b, contacting and raising a topportion of the sample tube 182 b above the other tubes in the sample box180 b. As a result, the gripper head 1225 has sufficient clearance toengage with the sample tube 182. The gripper head 1225 then grips thetop of the sample tube 182 b and lifts the sample tube 182 b up and outof the sample box 180 b.

FIGS. 14A-B illustrate a portion of a tube picker robot 140 in anoperation scanning a sample ID of a sample tube. The scanning may occurafter the extraction operation described above with reference to FIG. 13. FIG. 14A illustrates a scan of a sample ID located at the side of asample tube 182 b. The gripper head 1225 may raise the sample tube 182 bpartially (or fully) outside of the working chamber 120 and rotate thesample tube 182 b to align a portion of the sample tube 182 b with aline-of-sight (LOS) of the ID reader 930. If the sample tube 182 b hasaccumulated frost covering the sample ID at the side of the tube, thenthe gripper head 1225 may first move the sample tube 182 b against abrush 932 located inside or outside the working chamber 120 to removethe frost. The ID reader 930 may include a plurality of differentreaders (e.g., a 1D barcode reader, a 2D barcode reader) in order toscan a range of different sample ID formats. Further, the ID reader 930may be implemented with one or more optical tools (e.g., mirrors,lenses) to facilitate visibility of the sample ID to the ID reader 930.For example, one or more mirrors may be positioned to reflect an imageof the sample ID at the sample tube to the ID reader 930 while thesample tube is located inside the working chamber 120, thereby allowingthe sample tube 182 b to be identified without exposing it to thenon-cryogenic environment outside of the working chamber 120. Followingthe ID scan, the picker robot 140 may proceed to control the gripperhead 1225 to transfer the sample tube 182 to a target slot in adestination sample box.

FIG. 14B illustrates a scan of a sample ID in a further embodiment. Inthis example, a sample ID is located at the bottom of the sample tube182 b. In order to read the sample ID, a mirror 931 may be positioned inor out of the working chamber 120 and below the ID reader 930 to providethe ID reader with a reflected bottom-up view of the sample tube 180 bwhen raised above the working chamber 120. The gripper head 1225 mayraise the sample tube 182 b outside of the working chamber 120 to alignthe bottom of the sample tube with the reflected line-of-sight of the IDreader 930. As a result, the ID reader 930 can scan the sample ID at thebottom of the sample tube 182 b.

FIG. 15 is a perspective view of a system 1500 including multiplefreezers. The system 1500 may include some or all of the features of thesystem 100 described above, including the transfer module 101 that isconfigured to move along the track 192. In contrast, the transfer moduleis configured to service up to two rows each of multiple automatedfreezers 1505 a-h, the rows being aligned at each side of the track 192.Each of the automated freezers 1505 a-h may include features of thefreezer 105 a, the rack puller 107 a and, optionally, the freezer port108 a described above. To service a selected one of the automatedfreezers 1505 a-h, the transfer module 101 may move along the track 192to align its freezer port with either the rack puller or freezer port ofthe selected freezer.

The system 1500 may also include an access panel 1510 that includes adoor 1520. When the transfer module 101 is positioned at the accesspanel 1510, it I/O port (e.g., I/O port 125) may be aligned with thedoor 1520, thereby enabling a user to access the I/O port through thedoor 1520 to add or remove samples at the I/O port. The system 1500 as awhole may be encompassed by adjoining walls (e.g., implemented in aclosed room) to ensure user safety during operation.

FIG. 16A illustrates a system 1600 in a further embodiment. The system1600 may include some or all of the features of the system 100 describedabove, but in a configuration that maintains a working chamber as astationary module. The transfer station 1650 may encompass some or allfeatures of the working chamber 120, intermediate chamber 115,automation station 900, ID reader 930, and picker robot 130. Thetransport module 1601 may encompass some or all features of thetransport chamber 110, box transport robot 130, rail assembly 132, I/Oport 125, and I/O module 950 described above, and may further include acache for temporarily storing sample boxes during a transport operation.In further embodiments, the transport module 1601 may also include someor all features of the freezer port 108 a described above.

In an example operation, the transport module 1601 may move along atrack 1692 to align with a selected automated freezer (e.g., freezer1605 a, which may include the features of the freezer 105 a, rack puller107 a and freezer port 108 a described above). The transport module 1601obtains a sample box from the freezer 1605 a and stores it to a cache.The transport module 1601 then moves along the track 1692 to align withthe transfer station 1650, and transports the selected sample box (and,optionally, other sample boxes) into a working chamber of the transferstation 1650. The transfer station 1650, utilizing a picker robot, mayperform a transfer of selected sample tubes between the selected samplebox and one or more other sample boxes as described above. Once thesample tube transfer is complete, the transport module 1601 may retrievethe selected sample box and return it to the freezer 1605 a, or maytransport it to a different freezer, or to a user via an integrated orstandalone I/O port.

By maintaining a stationary working chamber, the transfer station maysimplify maintenance of the cryogenic environment within it. Inaddition, the transport module 1601, by omitting some elements of thetransfer module 101 described above, may occupy less space and mass thanthe transfer module 101, thereby simplifying movement and accommodatinga compact arrangement of the components of system 1600.

FIG. 16B illustrates the transport module 1601 in further detail, with afront cover removed. The transport module 1601 may include a boxtransport robot 1630 that may include some or all features of the boxtransport robot 130 and rail assembly 132 described above. The boxtransport robot 1630 may operate to transport sample boxes (e.g., samplebox 180 b as shown) between doors (interfacing with the freezers 1605a-d) 1608 a-b and a cache 1640.

FIG. 16C illustrates the box transport module 1601 and the cache 1640 infurther detail. The cache 1640 may include some features of the workingchamber 120 described above. For example, the cache 1640 may include aplatform 1641 that forms a plurality of support surfaces 1642 a-d, eachsupport surface being configured to support a respective sample box suchas the sample box 180 b as shown at the support surface 1642 a. Thecache 1640 may also maintain a cryogenic environment, and may do so bycontaining a volume of a liquid coolant (e.g., liquid nitrogen).Alternatively, the cache may be configured to maintain a temperatureabove a cryogenic temperature, provided that the samples can bemaintained at an acceptable temperature (e.g., below a respective glasstransition temperature) for the duration of their time stored at thecache 1640. An automated door 1645 provides passage to the cache 1640,and can be sealed outside of access by the box transport robot 1630 tomaintain the environment of the cache 1640.

While example embodiments have been particularly shown and described, itwill be understood by those skilled in the art that various changes inform and details may be made therein without departing from the scope ofthe embodiments encompassed by the appended claims.

What is claimed is:
 1. A cryogenic storage system, comprising: afreezer, the freezer coupled to a freezer port; the freezer portconfigured to receive a first sample box extracted from the freezer; aworking chamber configured to maintain a cryogenic environment, whereinthe working chamber is configured to enable the selection and transferof individual sample tubes between sample boxes within the workingchamber; an input/output (I/O) port configured to enable external accessto samples; a box transport robot configured to transport the firstsample box between the at least one freezer port, the working chamber,and the I/O port; a picker robot configured to transport, within theworking chamber, a sample tube between the first sample box and a secondsample box; a transport chamber, the transport chamber being coupled tothe at least one freezer port during access by the box transport robot,the transport chamber housing the box transport robot; and anintermediate chamber coupled between the transport chamber and theworking chamber, the intermediate chamber housing at least a portion ofthe picker robot, the box transport robot being configured to transportthe first sample box through the intermediate chamber to the workingchamber.
 2. The system of claim 1, further comprising an ejectorconfigured to transport the first sample box through at least a portionof the at least one freezer port to a position accessible to the boxtransport robot.
 3. The system of claim 2, wherein the ejector includesa pair of arms configured to move and guide opposite sides to controlpositioning of the first sample box.
 4. The system of claim 2, whereinthe ejector includes a floor configured to support the first sample box,at least a portion of the floor being depressible via a force applied bythe box transport robot.
 5. The system of claim 2, wherein the ejectoris configured to transport a plurality of different sample box formats.6. The system of claim 1, wherein the transport chamber is furtherconfigured to maintain an environment above a glass transitiontemperature of samples of the first sample box.
 7. The system of claim1, wherein the transport chamber is connected to the working chamber viaan aperture.
 8. The system of claim 7, wherein the box transport robotis configured to extend into the working chamber via the aperture duringtransport of the first sample box.
 9. The system of claim 7, wherein thepicker robot is configured to extend into the working chamber via theaperture during transport of the sample tube.
 10. The system of claim 1,wherein the box transport robot further includes a box gripper assemblyconfigured to grip the first sample box.
 11. The system of claim 10,wherein the box gripper assembly includes a pair of arms configured toclamp opposing corners of the first sample box, each of the pair of armsincluding a set of contact points adapted to accommodate a plurality ofsample box formats, the pair of arms being further configured to adjustthe first sample box to a target rotational and positional orientation.12. The system of claim 11, wherein at least one of the sets of contactpoints define a W shape, a first portion of the W shape accommodates afirst sample box format, and a second portion of the W shapeaccommodates a second sample box format.
 13. The system of claim 10,wherein the box transport robot includes a rail assembly on which thebox gripper assembly moves.
 14. The system of claim 1, wherein thepicker robot includes a first arm including a tube gripper assembly anda second arm including a push-up pin.
 15. The system of claim 14,wherein the second arm extends under a platform supporting sample boxesin the working chamber, the second arm being configured to drive thepush-up pin into the first sample box to raise a portion of the sampletube from the first sample box.
 16. The system of claim 14, wherein thetube gripper assembly includes a plurality of teeth, the tube gripperassembly configured to rotate horizontally the plurality of teeth aroundand toward a center axis to grip the sample tube.
 17. The system ofclaim 16, wherein the teeth are thermally isolated from components ofthe picker robot external to the working chamber via a thermalinsulator.
 18. The system of claim 14, wherein the first arm isconfigured to move the sample tube to a position enabling anidentification (ID) tag of the sample tube to be read by an ID reader.19. The system of claim 18, wherein the position is external to theworking chamber.
 20. The system of claim 18, wherein the first arm isfurther configured to 1) pass the sample tube along a cleaner to removefrost from the sample tube and 2) rotate the sample tube to align the IDtag with the ID reader.
 21. The system of claim 18, wherein the positionenables the ID tag to be read by the ID reader via a reflection of theID tag from a mirror.
 22. The system of claim 1, wherein the workingchamber includes a platform configured to support the first and secondsample boxes.
 23. The system of claim 22, further comprising a clampassembly configured to secure the first sample box via a force appliedto a corner of the first sample box, the clamp including a set ofcontact points adapted to accommodate a plurality of sample box formats.24. The system of claim 23, wherein the set of contact points define a Wshape, a first portion of the W shape accommodates a first sample boxformat, and a second portion of the W shape accommodates a second samplebox format.
 25. The system of claim 22, wherein the platform includes anaperture exposing a portion of a bottom surface of the first sample box,the aperture enabling access to a bottom of the sample tube by the tubepicker robot.
 26. The system of claim 22, wherein the working chamber isfurther configured to contain a liquid coolant below the platform. 27.The system of claim 26, further comprising a heat sink coupled to theplatform and configured to be partially immersed in the liquid coolant.28. The system of claim 26, wherein the tube picker robot includes anarm supporting a push-up pin, the arm configured to be at leastpartially immersed in the liquid coolant.
 29. The system of claim 1,further including a light curtain configured to detect a format of athird sample box at the I/O port.
 30. The system of claim 29, whereinthe light curtain projects a single collimated light source.
 31. Thesystem of claim 1, wherein the at least one freezer port includes aplurality of freezer ports, each of the plurality of freezer ports beingconfigured to receive sample boxes extracted from a respective freezer.32. The system of claim 1, further comprising a rail assembly configuredto move the at least one freezer port between a plurality of freezers.33. The system of claim 32, wherein the rail assembly is furtherconfigured to move the working chamber, the box transport robot, and thetube picker robot in unison with the at least one freezer port.
 34. Thesystem of claim 1, wherein the at least one freezer port is configuredto connect with an extractor assembly, the extractor assembly beingconfigured to raise a storage rack from a freezer and eject the firstsample box from the rack.
 35. A method of transporting a sample,comprising: extracting a first sample box from a respective freezer viaa freezer port; transporting the first sample box, via a box transportrobot, from the freezer port to a transport chamber coupled to thefreezer port during access by the box transport robot, the transportchamber housing the box transport robot; transporting the first samplebox, via the box transport robot, from the transport chamber to anintermediate chamber coupled between the transport chamber and a workingchamber configured to maintain a cryogenic environment and configured toenable the selection and transfer of individual sample tubes betweensample boxes within the working chamber, the intermediate chamberhousing at least a portion of a picker robot; transporting the firstsample box, via the box transport robot, from the intermediate chamberto the working chamber; and transporting, via the picker robot withinthe working chamber, a sample tube between the first sample box and asecond sample box.
 36. The method of claim 35, further comprisingtransporting the first sample box, via the box transport robot, from theworking chamber to an I/O port configured to enable external access tosamples.
 37. The method of claim 35, wherein the working chamberincludes a platform configured to support a plurality of sample boxesincluding the first sample box and the second sample box.
 38. The methodof claim 37, wherein the working chamber is further configured tocontain a liquid coolant below the platform.
 39. The method of claim 38,further comprising a heat sink coupled to the platform and configured tobe partially immersed in the liquid coolant.
 40. The method of claim 38,wherein the tube picker robot includes an arm supporting a push-up pin,the arm configured to be at least partially immersed in the liquidcoolant.
 41. The method of claim 35, further comprising: picking thesample tube in the working chamber using the picker robot; removingfrost from the sample tube while the sample tube is at least partiallywithin the cryogenic environment of the working chamber; and reading theindicia from the sample tube.